Liver transplantation is an effective and widely accepted therapy for children with end-stage liver disease. Major indications include primary liver disease, resulting in hepatic insufficiency, or severe morbidity secondary to chronic non-progressive liver disease and metabolic diseases of the liver. Liver replacement should not be considered if there is an acceptable alternative therapy. Relative contraindications to transplantation include irreversible impairment of other organ systems, major systemic infection and diseases expected to recur after transplantation. Early referral for pre-transplant evaluation is important to confirm the proper diagnosis and determine priority for transplantation, to identify potential contraindications, and to assist in supportive care of the patient with chronic liver disease. Innovations such as reduced-sized liver grafts and most recently, living related liver transplantation have increased the donor supply of organs for small infants and significantly reduced pre-transplant mortality. In addition, living donor transplantation allows infants to benefit from transplantation before developing severe complications of end-stage liver disease and reduces the incidence of primary graft non-function and rejection. Immunosuppression following transplantation is maintained with methylprednisolone, azathioprine and cyclosporine. Acute rejection is treated with short bursts of high-dose corticosteroids and when necessary OKT3. With this approach, 90% of the episodes of rejection can be successfully controlled. Survival after transplantation has steadily improved and survival rates of 70%-90% are routine. Following transplantation, children experience rapid nutritional restoration, increased muscle strength, marked progress in gross motor development and improved general health.